The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Stimulation of Lipolysis and Hormone-sensitive Lipase via the Extracellular Signal-regulated Kinase Pathway
Open accessAbstract
Hormonally stimulated lipolysis occurs by activation of cyclic AMP-dependent protein kinase (PKA) which phosphorylates hormone-sensitive lipase (HSL) and increases adipocyte lipolysis. Evidence suggests that catecholamines not only can activate PKA, but also the mitogen-activated protein kinase pathway and extracellular signal-regulated kinase (ERK). We now demonstrate that two different inhibitors of MEK, the upstream activator of ERK, block catecholamine- and beta(3)-stimulated lipolysis by approximately 30%. Furthermore, treatment of adipocytes with dioctanoylglycerol, which activates ERK, increases lipolysis, although MEK inhibitors decrease dioctanoylglycerol-stimulated activation of lipolysis. Using a tamoxifen regulatable Raf system expressed in 3T3-L1 preadipocytes, exposure to tamoxifen causes a 14-fold activation of ERK within 15-30 min and results in approximately 2-fold increase in HSL activity. In addition, when differentiated 3T3-L1 cells expressing the regulatable Raf were exposed to tamoxifen, a 2-fold increase in lipolysis is observed. HSL is a substrate of activated ERK and site-directed mutagenesis of putative ERK consensus phosphorylation sites in HSL identified Ser(600) as the site phosphorylated by active ERK. When S600A HSL was expressed in 3T3-L1 cells expressing the regulatable Raf, tamoxifen treatment fails to increase its activity. Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.
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Cites
Gutkind, J. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.1839 · Cited by 812
Cited by
Khovidhunkit, W., Kim, M.-S., Memon, R. A., Shigenaga, J. K., Moser, A. H., Feingold, K. R., & Grunfeld, C. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300019-jlr200 · Cited by 1,481
Copps, K. D., & White, M. F. (2012) · Diabetologia · doi:10.1007/s00125-012-2644-8 · Cited by 1,017
“Potentially contributing to the latter finding, ERK1/2 can promote lipolysis and NEFA-mediated insulin resistance, both by downregulating adipocyte perilipin [120] and activating hormone-sensitive lipase [121].”
BackgroundAdipose triglyceride lipase and the lipolytic catabolism of cellular fat stores.
Zechner, R., Kienesberger, P. C., Haemmerle, G., Zimmermann, R., & Lass, A. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800031-jlr200 · Cited by 576
Kraemer, F. B., & Shen, W.-J. (2002) · Journal of Lipid Research · doi:10.1194/jlr.r200009-jlr200 · Cited by 511
Self-citationSkeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance
Kiens, B. (2006) · Physiological Reviews · doi:10.1152/physrev.00023.2004 · Cited by 478
Signalling Mechanisms Regulating Lipolysis
Carmen, G.-Y., & Víctor, S.-M. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2005.08.009 · Cited by 429
The Regulation of Fat Metabolism during Aerobic Exercise
Muscella, A., Stefàno, E., Lunetti, P., Capobianco, L., & Marsigliante, S. (2020) · Biomolecules · doi:10.3390/biom10121699 · Cited by 237
Lipid droplets and steroidogenic cells
Shen, W.-J., Azhar, S., & Kraemer, F. B. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.11.024 · Cited by 175
Self-citationRoepstorff, C., Donsmark, M., Thiele, M., Vistisen, B., Stewart, G., Vissing, K., Schjerling, P., Hardie, D. G., Galbo, H., & Kiens, B. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00097.2006 · Cited by 118
Roepstorff, C., Vistisen, B., Donsmark, M., Nielsen, J. N., Galbo, H., Green, K. A., Hardie, D. G., Wojtaszewski, J. F. P., Richter, E. A., & Kiens, B. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.066480 · Cited by 94
Modulation of myocellular fat stores: lipid droplet dynamics in health and disease
Meex, R. C. R., Schrauwen, P., & Hesselink, M. K. C. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.91053.2008 · Cited by 65
Triacylglycerol lipases and metabolic control: implications for health and disease
Watt, M. J., & Spriet, L. L. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00698.2009 · Cited by 66
Lipid droplets as signaling platforms linking metabolic and cellular functions
Arrese, E. L., Saudale, F. Z., & Soulages, J. L. (2014) · Lipid Insights · doi:10.4137/lpi.s11128 · Cited by 54
Saez-Lopez, C., Villena, J. A., Simó, R., & Selva, D. M. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108480 · Cited by 38
Ogasawara, J., Izawa, T., Sakurai, T., Sakurai, T., Shirato, K., Ishibashi, Y., Ishida, H., Ohno, H., & Kizaki, T. (2015) · Journal of Obesity · doi:10.1155/2015/473430 · Cited by 31
Dong, M., Li, L., Li, G., Song, J., Liu, B., Liu, X., & Wang, M. (2020) · Food & Function · doi:10.1039/d0fo01436b · Cited by 26
Metadata
- Authors
- Greenberg, A. S., Shen, W.-J., Muliro, K., Patel, S., Souza, S. C., Roth, R. A., & Kraemer, F. B.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 276
- Issue
- 48
- Pages
- 45456-45461
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2041335773
- Cited by
- 363
- References
- 1
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
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